Less intensive antileukemic therapies (monotherapy and/or combination) for older adults with acute myeloid leukemia who are not candidates for intensive antileukemic therapy: A systematic review and meta-analysis.

INTRODUCTION: Elderly patients with acute myeloid leukemia not eligible for intensive antileukemic therapy are treated with less intensive therapies, uncertainty remains regarding their relative merits. OBJECTIVES: To compare the effectiveness and safety of less intensive antileukemic therapies for older adults with newly diagnosed AML not candidates for intensive therapies. METHODS: We included randomized controlled trials (RCTs) and non-randomized studies (NRS) comparing less intensive therapies in adults over 55 years with newly diagnosed AML. We searched MEDLINE and EMBASE from inception to August 2021. We assessed risk of bias of RCTs with a modified Cochrane Risk of Bias tool, and NRS with the Non-Randomized Studies of Interventions tool (ROBINS-I). We calculated pooled hazard ratios (HRs), risk ratios (RRs), mean differences (MD) and their 95% confidence intervals (CIs) using a random-effects pairwise meta-analyses and assessed the certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. RESULTS: We included 27 studies (17 RCTs, 10 NRS; n = 5,698), which reported 9 comparisons. Patients were treated with azacitidine, decitabine, and low-dose cytarabine (LDAC), as monotherapies or in combination with other agents. Moderate certainty of evidence suggests no convincing difference in overall survival of patients who receive azacitidine monotherapy compared to LDAC monotherapy (HR 0.69; 95% CI, 0.31-1.53), fewer febrile neutropenia events occurred between azacitidine monotherapy to azacitidine combination (RR 0.45; 95% CI, 0.31-0.65), and, fewer neutropenia events occurred between LDAC monotherapy to decitabine monotherapy (RR 0.62; 95% CI 0.44-0.86). All other comparisons and outcomes had low or very low certainty of evidence. CONCLUSION: There is no convincing superiority in OS when comparing less intensive therapies. Azacitidine monotherapy is likely to have fewer adverse events than azacitidine combination (febrile neutropenia), and LDAC monotherapy is likely to have fewer adverse events than decitabine monotherapy (neutropenia).

Development and design validation of a novel network meta-analysis presentation tool for multiple outcomes: a qualitative descriptive study.

OBJECTIVE: The Grades of Recommendations, Assessment, Development and Evaluation working group recently developed an innovative approach to interpreting results from network meta-analyses (NMA) through minimally and partially contextualised methods; however, the optimal method for presenting results for multiple outcomes using this approach remains uncertain. We; therefore, developed and iteratively modified a presentation method that effectively summarises NMA results of multiple outcomes for clinicians using this new interpretation approach. DESIGN: Qualitative descriptive study. SETTING: A steering group of seven individuals with experience in NMA and design validation studies developed two colour-coded presentation formats for evaluation. Through an iterative process, we assessed the validity of both formats to maximise their clarity and ease of interpretation. PARTICIPANTS: 26 participants including 20 clinicians who routinely provide patient care, 3 research staff/research methodologists and 3 residents. MAIN OUTCOME MEASURES: Two team members used qualitative content analysis to independently analyse transcripts of all interviews. The steering group reviewed the analyses and responded with serial modifications of the presentation format. RESULTS: To ensure that readers could easily discern the benefits and safety of each included treatment across all assessed outcomes, participants primarily focused on simple information presentations, with intuitive organisational decisions and colour coding. Feedback ultimately resulted in two presentation versions, each preferred by a substantial group of participants, and development of a legend to facilitate interpretation. CONCLUSION: Iterative design validation facilitated the development of two novel formats for presenting minimally or partially contextualised NMA results for multiple outcomes. These presentation approaches appeal to audiences that include clinicians with limited familiarity with NMAs.

Health Related Values and Preferences Regarding Meat Intake: A Cross-Sectional Mixed-Methods Study.

BACKGROUND: In addition to social and environmental determinants, people's values and preferences determine daily food choices. This study evaluated adults' values and preferences regarding unprocessed red meat (URM) and processed meat (PM) and their willingness to change their consumption in the face of possible undesirable health consequences. METHODS: A cross-sectional mixed-methods study including a quantitative assessment through an online survey, a qualitative inquiry through semi-structured interviews, and a follow-up assessment through a telephone survey. We performed descriptive statistics, logistic regressions, and thematic analysis. RESULTS: Of 304 participants, over 75% were unwilling to stop their consumption of either URM or PM, and of those unwilling to stop, over 80% were also unwilling to reduce. Men were less likely to stop meat intake than women (odds ratios < 0.4). From the semi-structured interviews, we identified three main themes: the social and/or family context of meat consumption, health- and non-health-related concerns about meat, and uncertainty of the evidence. At three months, 63% of participants reported no changes in meat intake. CONCLUSIONS: When informed about the cancer incidence and mortality risks of meat consumption, most respondents would not reduce their intake. Public health and clinical nutrition guidelines should ensure that their recommendations are consistent with population values and preferences.

How do cancer screening guidelines trade off benefits versus harms and burdens of screening? A systematic survey.

OBJECTIVES: Cancer screening guidelines differ in their recommendations for or against screening. To be able to provide explicit recommendations, guidelines need to specify thresholds for the magnitude of benefits of screening, given its harms and burdens. We evaluated how current cancer screening guidelines address the relative importance of benefits versus harms and burdens of screening. DATA SOURCE: We searched the Guidelines International Network, International Guideline Library, ECRI Institute and Medline. Two pairs of reviewers independently performed guideline selection and data abstraction. ELIGIBILITY CRITERIA: We included all cancer screening guidelines published in English between January 2014 and April 2019. RESULTS: Of 68 eligible guidelines, 25 included a statement regarding the trade-off between screening benefits versus harms and burdens (14 guidelines), or a statement of direction of the net effect (defined as benefits minus harms or burdens) (13 guidelines). None of these 25 guidelines defined how large a screening benefit should be to recommend screening, given its harms and burdens. 11 guidelines performed an economic evaluation of screening. Of these, six identified a key benefit outcome; two specified a cost-effectiveness threshold for recommending a screening option. Eight guidelines commented on people's values and preferences regarding the trade-off between benefits versus harms and burdens. CONCLUSIONS: Current cancer screening guidelines fail to specify the values and preferences underlying their recommendations. No guidelines provide a threshold at which they believe the benefits of screening outweigh its harms and burdens. PROSPERO REGISTRATION NUMBER: CRD42019138590.

Evaluating adults' health-related values and preferences about unprocessed red meat and processed meat consumption: protocol for a cross-sectional mixed-methods study.

Background: People need to choose from a wide range of foods, and in addition to availability and accessibility, people's values and preferences largely determine their daily food choices. Given the potential adverse health consequences of red and processed meat and the limited knowledge on individuals' health-related values and preferences on the topic, such data would be useful in the development of recommendations regarding meat consumption. Methods and analysis: We will perform an international cross-sectional mixed methods study in four countries across two continents. The study population will consist of adult omnivores currently consuming a minimum of three weekly servings of either unprocessed red meat or processed meat. We will explore participants' willingness to stop or reduce their unprocessed red meat, or their processed meat consumption through a direct-choice exercise. This exercise will consist of presenting a scenario tailored to each individual's average weekly consumption. That is, based on a systematic review and meta-analysis of the best estimate of the risk reduction in overall cancer mortality and cancer incidence, we will ask participants if they would stop their consumption, and/or reduce their average consumption. We will also present the corresponding certainty of the evidence for the potential risk reductions. Finally, for all included participants, we will measure their meat consumption three months after the interview and determine if they have made any changes to their average consumption. Ethics and dissemination: The research protocol was approved by the ethics committees in Canada (Research Ethics Board, Dalhousie University), Spain (Comitè Ètic d'Investigació Clínica de l'IDIAP Jordi Gol), Poland (The Bioethics Committee of the Jagiellonian University), and Brazil (National Research Ethics Commission). The study is based on voluntary participation and informed written consent. Results from this project will be disseminated through publications and presentations.